At least three Nogo isoforms are generated by alternative splicing of transcripts derived form the NogoA gene. The C-terminal third of all three isoforms shares high homology (approximately 70% at the amino acid level) with the reticulon protein family. NogoA, the largest isoform, has been shown to inhibit axon regeneration in culture. It is thought that the normal role of Nogo proteins is to prevent axon sprouting in the uninjured central nervous system. NogoA is localised to central nervous system myelin and is highly expressed in oligodendrocytes; NogoB and NogoC are expressed in some neurons and several non-neural tissues. All Nogo isoforms surprisingly have a C-terminal ER-retention motif but at least some NogoA protein is thought to reach the cell surface. All 3 Nogo isoforms have 2 potential trans-membrane domains. Both the C and N termini may be cytoplasmically exposed and a 66 amino acid loop separated by the TM domains may be located extracellularly.
An aspartyl protease called BACE (also known as Asp2 or memapsin2) has recently been shown to be responsible for β-secretase activity in relation to amyloid precursor protein (APP) processing. BACE is a type I transmembrane protein with a large lumenal domain containing the protease domain.